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Gene expression profiling of skeletal muscle in exercise-trained and sedentary rats with inborn high and low VO_2max

¹ Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
² Istituto Tecnologie Biomediche - Consiglio Nazionale delle Ricerche, Segrate, Milan
³ IRCCS Multimedica, Scientific and Technology Pole, Milan, Italy
⁴ Department of Mathematical Sciences, NTNU, Trondheim, Norway
⁵ Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, United Kingdom
⁶ Department of Cancer Research and Molecular Medicine, NTNU, Trondheim, Norway
⁷ Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, Michigan
⁸ Department of Cardiology, St. Olav's Hospital, Trondheim, Norway

The relationship between inborn maximal oxygen uptake (VO_2max) and skeletal muscle gene expression is unknown. Since low VO_2max is a strong predictor of cardiovascular mortality, genes related to low VO_2max might also be involved in cardiovascular disease. To establish the relationship between inborn VO_2max and gene expression, we performed microarray analysis of the soleus muscle of rats artificially selected for high- and low running capacity (HCR and LCR, respectively). In LCR, a low VO_2max was accompanied by aggregation of cardiovascular risk factors similar to the metabolic syndrome. Although sedentary HCR were able to maintain a 120% higher running speed at VO_2max than sedentary LCR, only three transcripts were differentially expressed (FDR 0.05) between the groups. Sedentary LCR expressed high levels of a transcript with strong homology to human leucyl-transfer RNA synthetase, of whose overexpression has been associated with a mutation linked to mitochondrial dysfunction. Moreover, we studied exercise-induced alterations in soleus gene expression, since accumulating evidence indicates that long-term endurance training has beneficial effects on the metabolic syndrome. In terms of gene expression, the response to exercise training was more pronounced in HCR than LCR. HCR upregulated several genes associated with lipid metabolism and fatty acid elongation, whereas LCR upregulated only one transcript after exercise training. The results indicate only minor differences in soleus muscle gene expression between sedentary HCR and LCR. However, the inborn level of fitness seems to influence the transcriptional adaption to exercise, as more genes were upregulated after exercise training in HCR than LCR.

microarray analysis; gene ontology; metabolic syndrome; MELAS; soleus muscle

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